Browsing by Author "Ranjana Patnaik"

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Alzheimer's disease neuropathology is exacerbated following traumatic brain injury. Neuroprotection by co-administration of nanowired mesenchymal stem cells and cerebrolysin with monoclonal antibodies to amyloid beta peptide
(Elsevier B.V., 2021) Hari Shanker Sharma; Dafin F. Muresanu; Rudy J. Castellani; Ala Nozari; José Vicente Lafuente; Anca D. Buzoianu; Seaab Sahib; Z. Ryan Tian; Igor Bryukhovetskiy; Igor Manzhulo; Preeti K. Menon; Ranjana Patnaik; Lars Wiklund; Aruna Sharma
Military personnel are prone to traumatic brain injury (TBI) that is one of the risk factors in developing Alzheimer's disease (AD) at a later stage. TBI induces breakdown of the blood-brain barrier (BBB) to serum proteins into the brain and leads to extravasation of plasma amyloid beta peptide (ΑβP) into the brain fluid compartments causing AD brain pathology. Thus, there is a need to expand our knowledge on the role of TBI in AD. In addition, exploration of the novel roles of nanomedicine in AD and TBI for neuroprotection is the need of the hour. Since stem cells and neurotrophic factors play important roles in TBI and in AD, it is likely that nanodelivery of these agents exert superior neuroprotection in TBI induced exacerbation of AD brain pathology. In this review, these aspects are examined in details based on our own investigations in the light of current scientific literature in the field. Our observations show that TBI exacerbates AD brain pathology and TiO2 nanowired delivery of mesenchymal stem cells together with cerebrolysin—a balanced composition of several neurotrophic factors and active peptide fragments, and monoclonal antibodies to amyloid beta protein thwarted the development of neuropathology following TBI in AD, not reported earlier. © 2021 Elsevier B.V.
Bilateral Common Carotid Artery Occlusion: Stroke Model
(Springer Singapore, 2021) Chandra Kant Singh Tekam; Saksha Shinde; Ranjana Patnaik; Sanjeev Kumar Mahto
Ischemic stroke is a prime spawn of death, physical disability and imparts an immense socioeconomic burden for society. Despite, rigorous experimental and clinical research work over the past few decades, still, therapeutic options are scarce for patients with acute ischemic stroke (AIS). It caused an increase in the percentage of ischemic patients in the ensuing years. One approach is to develop a better understanding of the brain’s cellular and molecular mechanisms to combat this harmful problem. One of the extensively used approaches for Brain-induced neuroprotection is ischemic preconditioning (IPC) or ischemic tolerance (IT). IPC is a non-harmful stimulus applied to the brain, which leads to interim resistance in the wake of ischemic insult. The IPC takes place in two different categories: initial IT, which lasts from a few minutes to a few hours after the IPC, and delayed IT, which takes a couple of hours to occur. Until now, the investigation has focused on delayed IT but the molecular mechanism of IT is largely unknown. This chapter aims to provide insight into Bilateral Common Carotid Aartery Occlusion (BCCAO) methodology and factors affecting the biological pathways in the course of neurodegeneration in rodents (mice and rats). © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021.
Blood-Central Nervous System Barriers in Morphine Dependence and Withdrawal
(Elsevier Inc., 2004) Hari Shanker Sharma; Ranjana Patnaik; Amit Kumar Ray; Prasanta Kumardey
The status of blood-central nervous system barriers during morphine dependence or withdrawal is still unknown. Morphine withdrawal is associated with profound stress response, immediate early gene expression in the CNS and alterations in neurochemical metabolism. Thus, a possibility exists that stress caused by morphine withdrawal will impair blood-CNS barriers function. Experiments carried out in our laboratory show that spontaneous morphine withdrawal in rats is associated with a selective and specific breakdown of the blood-brain, blood-CSF and blood-spinal cord barriers to Evans blue albumin, radioactive iodine and lanthanum (La3+) tracers. Several brain regions show pronounced structural alterations during morphine dependence and withdrawal. Pharmacological manipulations of nitric oxide (NO), serotonin (5-hydroxytryptamine) or Ca2+ channel during morphine dependence and withdrawal attenuates the blood-CNS barrier dysfunction and structural changes. These observations suggest that morphine dependence and withdrawal is associated with alterations in CNS microfluid environment and cellular damage. The functional significance of these findings and the probable mechanisms are discussed. © 2004 Elsevier Inc. All rights reserved.
Corrigendum: Effect of chlorogenic acid supplementation in MPTP-intoxicated mouse(Front Pharmacol., (2018), 6, (9757), 10.3389/fphar.2018.00757)
(Frontiers Media S.A., 2023) Saumitra S. Singh; Sachchida N. Rai; Hareram Birla; Walia Zahra; Gaurav Kumar; Mallikarjuna R. Gedda; Neeraj Tiwari; Ranjana Patnaik; Rakesh K. Singh; Surya P. Singh
In the published article, there was an error in Figure 8 as published. The figure panels in Figure 8 were erroneously duplicated. The corrected Figure 8 and its caption appear below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. © 2023 Singh, Rai, Birla, Zahra, Kumar, Gedda, Tiwari, Patnaik, Singh and Singh.
Development of in vivo drug-induced neurotoxicity models
(Informa Healthcare, 2014) Hari S. Sharma; Preeti Menon; José Vicente Lafuente; Dafin F. Muresanu; Z Ryan Tian; Ranjana Patnaik; Aruna Sharma
Introduction: Neurotoxicity caused by diverse psychostimulant drugs, for example, methamphetamine, 3,4-methylenedioxy-methamphetamine, cocaine or morphine is a cause of concern to human populations especially the young generation across the world. These recreational drugs affect brain function severely leading to addiction and brain pathology. Use of psychostimulants may induce breakdown of the blood-brain barrier to serum proteins resulting in adverse brain microenvironment, edema cell injury or eventually neuronal death. Thus, there is an urgent need to find out detailed mechanisms of psychostimulants-induced neurotoxicity in vivo models for suitable therapeutic strategies to induce neuroprotection and also to help de-addiction in clinical situations.Areas covered: In this review, psychostimulants drugs-induced neurotoxicity is discussed in view of recent literature and the financial burden it may pose on our society due to rehabilitation and de-addiction. Furthermore, experimental evidences of drug-induced neuroprotection are also discussed.Expert opinion: Use of in vivo models of neurotoxicity caused by psychostimulants is discussed based on author's own research and to find suitable drugs that could induce neuroprotection including nanodelivery. Furthermore, novel therapeutic agents for de-addiction and reducing neurotoxicity following psychostimulants administration are presented. © 2014 Informa UK, Ltd.
Effect of chlorogenic acid supplementation in MPTP-intoxicated mouse
(Frontiers Media S.A., 2018) Saumitra S. Singh; Sachchida N. Rai; Hareram Birla; Walia Zahra; Gaurav Kumar; Mallikarjuna R. Gedda; Neeraj Tiwari; Ranjana Patnaik; Rakesh K. Singh; Surya P. Singh
Oxidative stress and neuroinflammation play a key role in dopaminergic (DA) neuronal degeneration, which results in the hindrance of normal ongoing biological processes in the case of Parkinson's disease. As shown in several studies, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, different behavioral parameters have suggested motor impairment and damage of antioxidant defence. Thus, some specific biological molecules found in medicinal plants can be used to inhibit the DA neuronal degeneration through their antioxidant and anti-inflammatory activities. With this objective, we studied chlorogenic acid (CGA), a naturally occurring polyphenolic compound, for its antioxidant and anti-inflammatory properties in MPTP-intoxicated mice. We observed significant reoccurrence of motor coordination and antioxidant defence on CGA supplementation, which has been in contrast with MPTP-injected mice. Moreover, in the case of CGA-treated mice, the enhanced expression of tyrosine hydroxylase (TH) within the nigrostriatal region has supported its beneficial effect. The activation of glial cells and oxidative stress levels were also estimated using inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) immunoreactivity within substantia nigra (SN) and striatum of MPTP-injected mice. Administration of CGA has prevented the neuroinflammation in SN by regulating the nuclear factor-κB expression in the MPTP-induced group. The significant release of certain pro-inflammatory mediators such as tumor necrosis factor-α and interleukin (IL)-1β has also been inhibited by CGA with the enhanced expression of anti-inflammatory cytokine IL-10. Moreover, reduced GFAP staining within the nigrostriatal region has supported the fact that CGA has significantly helped in the attenuation of astrocyte activation. Hence, our study has shown that CGA supplementation shows its therapeutic ability by reducing the oxidative stress and neuroinflammation in MPTP-intoxicated mice. © 2018 Singh, Rai, Birla, Zahra, Kumar, Gedda, Tiwari, Patnaik, Singh and Singh.
Exacerbation of brain pathology after partial restraint in hypertensive rats following SiO2 nanoparticles exposure at high ambient temperature
(Humana Press Inc., 2013) Hari S. Sharma; Dafin F. Muresanu; Ranjana Patnaik; Aruna Sharma
This investigation examines the possibility that exposure to silica dust of hypertensive individuals may exacerbate brain pathology and sensory motor dysfunction at high environmental temperature. Hypertension was produced in rats (200-250 g) by two-kidney one clip (2K1C) method, and in these animals, SiO2 nanoparticles (NPs; 50 to 60 nm) were administered at 50 mg/kg, i.p. daily for 1 week. On the 8th day, these rats were subjected to partial restraint in a Perspex box for 4 h either at room temperature (21 C) or at 33 C in a biological oxygen demand incubator (wind velocity, 2.6 cm/s; relative humidity, 65 to 67 %). In these animals, behavioral functions, blood-brain barrier (BBB) permeability to Evans blue albumin (EBA) and radioiodine ( [131]-Iodine), brain water content and neuronal injuries were determined. Hypertensive rats subjected to 4 h restraint at room temperature did not exhibit BBB dysfunction, brain edema, neural injury, or alterations in rotarod or inclined plane angle performances. However, when these hypertensive rats were subjected to restraint at 33 C, breakdown of the cortical BBB (EBA, +38 %; radioiodine, +56 %), brain water (+0.88 %), neuronal damages (+18 %), and behavioral impairment were exacerbated. Interestingly, SiO2 exposure to these rats further exacerbated BBB breakdown (EBA, 280 %; radioiodine, 350 %), brain edema (4 %), and neural injury (30 %) after identical restraint depending on the ambient temperature. SiO2 treatment also induced brain pathology and alteration in behavioral functions in normotensive rats after restraint at high temperature. These observations clearly show that hypertension significantly enhances restraint-induced brain pathology, and behavioral anomalies particularly at high ambient temperature and SiO 2 intoxication further exacerbated these brain pathologies and cognitive dysfunctions. © 2013 Springer Science+Business Media New York.
Histamine H3 and H4 receptors modulate Parkinson's disease induced brain pathology. Neuroprotective effects of nanowired BF-2649 and clobenpropit with anti-histamine-antibody therapy
(Elsevier B.V., 2021) Aruna Sharma; Dafin F. Muresanu; Ranjana Patnaik; Preeti K. Menon; Z. Ryan Tian; Seaab Sahib; Rudy J. Castellani; Ala Nozari; José Vicente Lafuente; Anca D. Buzoianu; Stephen D. Skaper; Igor Bryukhovetskiy; Igor Manzhulo; Lars Wiklund; Hari Shanker Sharma
Military personnel deployed in combat operations are highly prone to develop Parkinson's disease (PD) in later lives. PD largely involves dopaminergic pathways with hallmarks of increased alpha synuclein (ASNC), and phosphorylated tau (p-tau) in the cerebrospinal fluid (CSF) precipitating brain pathology. However, increased histaminergic nerve fibers in substantia nigra pars Compacta (SNpc), striatum (STr) and caudate putamen (CP) associated with upregulation of Histamine H3 receptors and downregulation of H4 receptors in human cases of PD is observed in postmortem cases. These findings indicate that modulation of histamine H3 and H4 receptors and/or histaminergic transmission may induce neuroprotection in PD induced brain pathology. In this review effects of a potent histaminergic H3 receptor inverse agonist BF-2549 or clobenpropit (CLBPT) partial histamine H4 agonist with H3 receptor antagonist, in association with monoclonal anti-histamine antibodies (AHmAb) in PD brain pathology is discussed based on our own observations. Our investigation shows that chronic administration of conventional or TiO2 nanowired BF 2649 (1 mg/kg, i.p.) or CLBPT (1 mg/kg, i.p.) once daily for 1 week together with nanowired delivery of HAmAb (25 μL) significantly thwarted ASNC and p-tau levels in the SNpC and STr and reduced PD induced brain pathology. These observations are the first to show the involvement of histamine receptors in PD and opens new avenues for the development of novel drug strategies in clinical strategies for PD, not reported earlier. © 2021 Elsevier B.V.
Identification of potential inhibitors of PARP-1, a regulator of caspase-independent cell death pathway, from Withania somnifera phytochemicals for combating neurotoxicity: A structure-based in-silico study
(World Scientific Publishing Co. Pte Ltd, 2017) Sumedha Mukherjee; Gaurav Kumar; Ranjana Patnaik
Poly (ADP-ribose) polymerase-1 (PARP-1) reverses DNA damage by repairing DNA nicks and breaks in the normal cellular environment. However, during abnormal conditions like stroke and other neurological disorders, overactivation of PARP-1 leads to neuronal cell death via a caspase-independent programmed cell death pathway. Strategies involving inhibition or knockout of PARP-1 have proved beneficial in combating neuro-cytotoxicity. In this study, we performed in-silico analysis of 27 phytochemicals of Withania somnifera (Ashwagandha), to investigate their inhibition efficiency against PARP-1. Out of 27 phytochemicals, we report 12 phytochemicals binding to the catalytic domain of PARP-1 with an affinity higher than FR257517, PJ34 and Talazoparib (highly potent inhibitors of the enzyme). Among these 12 compounds, five phytochemicals namely Stigmasterol, Withacnistin, Withaferin A, Withanolide G and Withanolide B show an exceptionally high binding affinity for the catalytic domain of PARP-1 and bind to the enzyme with similar hydrogen bond formation and hydrophobic interaction pattern as their inhibitors. All of these phytochemicals are BBB permeable so that they can be further developed into potential future neuro-Therapeutic drugs against neurodegenerative disorders involving neuronal cell death. © 2017 World Scientific Publishing Company.
Melatonin renders neuroprotection by protein kinase C mediated aquaporin-4 inhibition in animal model of focal cerebral ischemia
(Elsevier Inc., 2014) Pallab Bhattacharya; Anand Kumar Pandey; Sudip Paul; Ranjana Patnaik
Aim: Aquaporin-4(AQP4) expression in the brain with relation to edema formation following focal cerebral ischemia was investigated. Studies have shown that brain edema is one of the significant factors in worsening stroke outcomes. While many mechanisms may aggravate brain injury, one such potential system may involve AQP4 up regulation in stroke patients that could result in increased edema formation. Post administration of melatonin following ischemic stroke reduces AQP4 mediated brain edema and confers neuroprotection. Materials and methods: An in-silico approach was undertaken to confirm effective melatonin-AQP4 binding. Rats were treated with 5 mg/kg, i.p. melatonin or placebo at 30 min prior, 60 min post and 120 min post 60 min of middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion. Rats were evaluated for battery of neurological and motor function tests just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, biochemical analysis, apoptosis study and western blot experiments. Key findings: Melatonin at 60 min post ischemia rendered neuroprotection as evident by reduction in cerebral infarct volume, improvement in motor and neurological deficit and reduction in brain edema. Furthermore, ischemia induced surge in levels of nitrite and malondialdehyde (MDA) were also found to be significantly reduced in ischemic brain regions in treated animals. Melatonin potentiated intrinsic antioxidant status, inhibited acid mediated rise in intracellular calcium levels, decreased apoptotic cell death and also markedly inhibited protein kinase C (PKC) influenced AQP4 expression in the cerebral cortex and dorsal striatum. Significance: Melatonin confers neuroprotection by protein kinase C mediated AQP4 inhibition in ischemic stroke. © 2014 Elsevier Inc. All rights reserved.
Methamphetamine exacerbates pathophysiology of traumatic brain injury at high altitude. Neuroprotective effects of nanodelivery of a potent antioxidant compound H-290/51
(Elsevier B.V., 2021) Hari Shanker Sharma; José Vicente Lafuente; Lianyuan Feng; Dafin F. Muresanu; Preeti K. Menon; Rudy J. Castellani; Ala Nozari; Seaab Sahib; Z. Ryan Tian; Anca D. Buzoianu; Per-Ove Sjöquist; Ranjana Patnaik; Lars Wiklund; Aruna Sharma
Military personnel are often exposed to high altitude (HA, ca. 4500–5000 m) for combat operations associated with neurological dysfunctions. HA is a severe stressful situation and people frequently use methamphetamine (METH) or other psychostimulants to cope stress. Since military personnel are prone to different kinds of traumatic brain injury (TBI), in this review we discuss possible effects of METH on concussive head injury (CHI) at HA based on our own observations. METH exposure at HA exacerbates pathophysiology of CHI as compared to normobaric laboratory environment comparable to sea level. Increased blood-brain barrier (BBB) breakdown, edema formation and reductions in the cerebral blood flow (CBF) following CHI were exacerbated by METH intoxication at HA. Damage to cerebral microvasculature and expression of beta catenin was also exacerbated following CHI in METH treated group at HA. TiO2-nanowired delivery of H-290/51 (150 mg/kg, i.p.), a potent chain-breaking antioxidant significantly enhanced CBF and reduced BBB breakdown, edema formation, beta catenin expression and brain pathology in METH exposed rats after CHI at HA. These observations are the first to point out that METH exposure in CHI exacerbated brain pathology at HA and this appears to be related with greater production of oxidative stress induced brain pathology, not reported earlier. © 2021 Elsevier B.V.
Nanodelivery of oxiracetam enhances memory, functional recovery and induces neuroprotection following concussive head injury
(Elsevier B.V., 2021) Feng Niu; Aruna Sharma; Zhenguo Wang; Lianyuan Feng; Dafin F. Muresanu; Seaab Sahib; Z. Ryan Tian; José Vicente Lafuente; Anca D. Buzoianu; Rudy J. Castellani; Ala Nozari; Preeti K. Menon; Ranjana Patnaik; Lars Wiklund; Hari Shanker Sharma
Military personnel are the most susceptible to concussive head injury (CHI) caused by explosion, blast or missile or blunt head trauma. Mild to moderate CHI could induce lifetime functional and cognitive disturbances causing significant decrease in quality of life. Severe CHI leads to instant death and lifetime paralysis. Thus, further exploration of novel therapeutic agents or new features of known pharmacological agents are needed to enhance quality of life of CHI victims. Previous reports from our laboratory showed that mild CHI induced by weight drop technique causing an impact of 0.224 N results in profound progressive functional deficit, memory impairment and brain pathology from 5 h after trauma that continued over several weeks of injury. In this investigation we report that TiO2 nanowired delivery of oxiracetam (50 mg/kg, i.p.) daily for 5 days after CHI resulted in significant improvement of functional deficit on the 8th day. This was observed using Rota Rod treadmill, memory improvement assessed by the time spent in finding hidden platform under water. The motor function improvement is seen in oxiracetam treated CHI group by placing forepaw on an inclined mesh walking and foot print analysis for stride length and distance between hind feet. TiO2-nanowired oxiracetam also induced marked improvements in the cerebral blood flow, reduction in the BBB breakdown and edema formation as well as neuroprotection of neuronal, glial and myelin damages caused by CHI at light and electron microscopy on the 7th day after 5 days TiO2 oxiracetam treatment. Adverse biochemical events such as upregulation of CSF nitrite and nitrate, IL-6, TNF-a and p-Tau are also reduced significantly in oxiracetam treated CHI group. On the other hand post treatment of 100 mg/kg dose of normal oxiracetam in identical conditions after CHI is needed to show slight but significant neuroprotection together with mild recovery of memory function and functional deficits on the 8th day. These observations are the first to point out that nanowired delivery of oxiracetam has superior neuroprotective ability in CHI. These results indicate a promising clinical future of TiO2 oxiracetam in treating CHI patients for better quality of life and neurorehabilitation, not reported earlier. © 2021 Elsevier B.V.
Nanodelivery of traditional Chinese Gingko Biloba extract EGb-761 and bilobalide BN-52021 induces superior neuroprotective effects on pathophysiology of heat stroke
(Elsevier B.V., 2021) Seaab Sahib; Aruna Sharma; Dafin F. Muresanu; Zhiqiang Zhang; Cong Li; Z. Ryan Tian; Anca D. Buzoianu; José Vicente Lafuente; Rudy J. Castellani; Ala Nozari; Ranjana Patnaik; Preeti K. Menon; Lars Wiklund; Hari Shanker Sharma
Military personnel often exposed to high summer heat are vulnerable to heat stroke (HS) resulting in abnormal brain function and mental anomalies. There are reasons to believe that leakage of the blood-brain barrier (BBB) due to hyperthermia and development of brain edema could result in brain pathology. Thus, exploration of suitable therapeutic strategies is needed to induce neuroprotection in HS. Extracts of Gingko Biloba (EGb-761) is traditionally used in a variety of mental disorders in Chinese traditional medicine since ages. In this chapter, effects of TiO2 nanowired EGb-761 and BN-52021 delivery to treat brain pathologies in HS is discussed based on our own investigations. We observed that TiO2 nanowired delivery of EGb-761 or TiO2 BN-52021 is able to attenuate more that 80% reduction in the brain pathology in HS as compared to conventional drug delivery. The functional outcome after HS is also significantly improved by nanowired delivery of EGb-761 and BN-52021. These observations are the first to suggest that nanowired delivery of EGb-761 and BN-52021 has superior therapeutic effects in HS not reported earlier. The clinical significance in relation to the military medicine is discussed. © 2021 Elsevier B.V.
Nanodrug delivery by single-walled carbon nanotubes (SWCNTs) in the central nervous system induces neurotoxicity. Potential neuroprotective effects of Cerebrolysin
(Nano Science and Technology Institute, 2014) HariS Sharma; DafinF Muresanu; José Vicente Lafuente; Ranjana Patnaik; Z. Ryan Tian; Herbert Mos̈sler; Aruna Sharma
Our military personnel are often inflicted with brain or spinal cord injury during combat operations caused by gunshot, missile explosions, fall or direct blunt or sharp trauma to their CNS leading to life threatening illnesses. Recently, single-walled carbon nanotubes (SWCNTs) are used for nano drug delivery in cancer therapy however; SWCNTs induced neurotoxicity is not well known. In this innovation, we used Cerebrolsyin, a balanced composition of several neurotrophic factors and active peptide fragments in attenuating SWCNTs induced neurotoxicity in the rat central nervous system (CNS). These observations support the idea that co-administration of Cerebrolsyin with SWCNTs is needed to enhance the neuroprotective effects of nanodrug delivery using SWCNTs as a vehicle.
Nanowired delivery of mesenchymal stem cell reduces diabetes induced aggravation brain damage following heatstroke
(Nano Science and Technology Institute, 2014) Hari S. Sharma; Lianyuan Feng; José Vicente Lafuente; Dafin F. Muresanu; Z. Ryan Tian; Ranjana Patnaik; Aruna Sharma
Our military personnel are often exposed to combat operations in hot environments in summer months (40 to 42°C) that often lead to heatstroke. Since endocrine disorders e.g., diabetes could result from posttraumatic stress disorders (PTSD) in military populations; these soldiers are highly vulnerable to additional heat stress. Previous reports from our lab suggest that diabetic rats showed greater brain pathology after heat stress. This suggests that military personnel with diabetes in heat stress have higher brain pathology during combat stress or other activities. Since stem cells are known to induce neuroprotection we examined whether nanodelivery of mesenchymal stem cells (MSCs) could enhance the potential neuroprotective effects of stem cells and reduce the aggravation of brain pathology in heat stress in diabetic rat model. Our observations clearly show that nanodelivery of MSCs markedly attenuated heat stress induced brain pathology in diabetic rats.
Neuroprotective effect of chlorogenic acid in global cerebral ischemia-reperfusion rat model
(Springer Verlag, 2019) Gaurav Kumar; Sumedha Mukherjee; Pankaj Paliwal; Saumitra Sen Singh; Hareram Birla; Surya Pratap Singh; Sairam Krishnamurthy; Ranjana Patnaik
The ischemic cascade is initiated in the hypoperfused region of the brain that leads to neuronal cell death. Identification of multi-target inhibitor against prominent molecular mediators of ischemic cascade might be a suitable strategy to combat cerebral ischemic stroke. The present study is designed to evaluate the neuroprotective efficacy of chlorogenic acid (CGA) in the global cerebral ischemic rat model. The effective dose of CGA was evaluated on the basis of reduction in cerebral infarction area percentage, Evans blue extravasation, and restoration of brain water content. The expression of tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and caspase-3 was evaluated by immunohistochemistry and morphological and cellular alterations in the cortex were observed by brain histology. The level of glutamate, calcium, and nitrate in different regions of the brain, as well as cerebrospinal fluid (CSF), was evaluated. The level of calcium and nitrate was compared with ifenprodil—an antagonist of N-methyl-D-aspartate receptor (NMDAR) and 7-nitroindazole—an inhibitor of neuronal nitric oxide synthase (nNOS) respectively. Further, molecular docking was performed to compare the inhibition potential of CGA against NMDAR and nNOS with their inhibitors. Dose optimization results revealed that intranasal administration of CGA (10 mg/kg b.w.) significantly reduced the cerebral infarction area, Evans blue extravasation and restored the brain water content compared with ischemia group. It also significantly reduced the calcium, nitrate, and glutamate levels compared with ischemia group in the cortex, hippocampus cerebellum, and CSF. Immunohistochemical analysis revealed that CGA significantly reduced the expression of TNF-α, iNOS, and caspase-3 as compared with the ischemia group. In molecular docking study, CGA displayed similar binding interaction as that of Ifenprodil and 7-nitroindazole with NMDAR and nNOS respectively. The current findings suggest that the treatment with CGA confers neuroprotection in global ischemic insult by inhibiting and downregulating the different molecular markers of cerebral ischemia. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
Neuroprotective effects of insulin like growth factor-1 on engineered metal nanoparticles Ag, Cu and Al induced blood-brain barrier breakdown, edema formation, oxidative stress, upregulation of neuronal nitric oxide synthase and brain pathology
(Elsevier B.V., 2021) Hari Shanker Sharma; José Vicente Lafuente; Dafin F. Muresanu; Seaab Sahib; Z. Ryan Tian; Preeti K. Menon; Rudy J. Castellani; Ala Nozari; Anca D. Buzoianu; Per-Ove Sjöquist; Ranjana Patnaik; Lars Wiklund; Aruna Sharma
Military personnel are vulnerable to environmental or industrial exposure of engineered nanoparticles (NPs) from metals. Long-term exposure of NPs from various sources affect sensory-motor or cognitive brain functions. Thus, a possibility exists that chronic exposure of NPs affect blood-brain barrier (BBB) breakdown and brain pathology by inducing oxidative stress and/or nitric oxide production. This hypothesis was examined in the rat intoxicated with Ag, Cu or Al (50–60 nm) nanoparticles (50 mg/kg, i.p. once daily) for 7 days. In these NPs treated rats the BBB permeability, brain edema, neuronal nitric oxide synthase (nNOS) immunoreactivity and brain oxidants levels, e.g., myeloperoxidase (MP), malondialdehyde (MD) and glutathione (GT) was examined on the 8th day. Cu and Ag but not Al nanoparticles increased the MP and MD levels by twofold in the brain although, GT showed 50% decline. At this time increase in brain water content and BBB breakdown to protein tracers were seen in areas exhibiting nNOS positive neurons and cell injuries. Pretreatment with insulin like growth factor-1 (IGF-1) in high doses (1 μg/kg, i.v. but not 0.5 μg/kg daily for 7 days) together with NPs significantly reduced the oxidative stress, nNOS upregulation, BBB breakdown, edema formation and cell injuries. These novel observations demonstrate that (i) NPs depending on their metal constituent (Cu, Ag but not Al) induce oxidative stress and nNOS expression leading to BBB disruption, brain edema and cell damage, and (ii) IGF-1 depending on doses exerts powerful neuroprotection against nanoneurotoxicity, not reported earlier. © 2021 Elsevier B.V.
Pharmacokinetics and brain penetration study of chlorogenic acid in rats
(Taylor and Francis Ltd, 2019) Gaurav Kumar; Pankaj Paliwal; Sumedha Mukherjee; Nishant Patnaik; Sairam Krishnamurthy; Ranjana Patnaik
1. The present study is designed to investigate the brain distribution and plasma pharmacokinetics profiles of chlorogenic acid (CGA) after intranasal administration in Charles–Foster rats to evaluate whether the CGA molecules are transported directly via the nose-to-brain path. 2. The CGA is administered intravenously (IV) and intranasally (IN) at the dose of 10 mg/kg. Further, its concentration in the plasma, cerebrospinal fluid (CSF) and the whole brain is analyzed by HPLC-UV method. 3. The study observes that CGA is rapidly absorbed in plasma with t max of 1 min similar to IV route after IN administration. The peak plasma concentration and AUC 0–24 are higher by 3.5 and 4.0 times respectively in IV administration, compared to IN delivery that represents the significant less systemic exposure of CGA in IN route. 4. However, the concentration of CGA in the brain is 4, 6.5, 5.3, 5.2 and 4.5 times higher at 30, 60, 120, 240 and 360 min, respectively in IN administration compared to IV administration. The exposure of CGA in the brain after IN administration (AUC brain, IN ) was significantly greater (4 times) as compared to the exposure of CGA in the brain (AUC brain, IV ) after IV administration reflecting significant brain uptake of CGA through nasal route. Therefore, IN delivery of CGA can be a promising approach for the treatment of stroke and neurodegenerative disorders. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
Quercetin in Hypoxia-Induced Oxidative Stress: Novel Target for Neuroprotection
(Academic Press Inc., 2012) Anand Kumar Pandey; Ranjana Patnaik; Dafin F. Muresanu; Aruna Sharma; Hari Shanker Sharma
Oxidative stress in the central nervous system is one of the key players for neurodegeneration. Thus, antioxidants could play important roles in treating several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and aging-related brain disorders. This review is focused on the new developments in oxidative stress-induced neurodegeneration. Further, based on our own investigations, new roles of quercetin, an antioxidant compound in hypoxia and ischemia induced neuroprotection in relation to suppression of oxidative stress, improvement in behavioral function, reduction in infarct volume, brain swelling, and cellular injury in both in vivo and in vitro models are discussed. Our new findings clearly suggest that antioxidant compounds have potential role in therapeutic strategies to treat neurodegenerative diseases in clinical settings. © 2012 Elsevier Inc.
Retraction Note to: Alleviation of glutamate-mediated neuronal insult by piroxicam in rodent model of focal cerebral ischemia: a possible mechanism of GABA agonism (Journal of Physiology and Biochemistry, (2014), 70, (901-913), 10.1007/s13105-014-0358-8)
(Springer Science and Business Media B.V., 2022) Pallab Bhattacharya; Anand Kumar Pandey; Sudip Paul; Ranjana Patnaik
The Editors-in-Chief have retracted this article because of anomalies in the images of brain sections presented in Figure 2a, namely: 7 panels in Figure 2a appear to be the same as panels in Figure 2a of a previous article [1] 2 panels in Figure 2a appear to be the same as panels in Figure 2a of a previous article [2] 2 panels in Figure 2a appear to be the same as panels in Figure 2a and 1 panel appears to be the same as a panel in Figure 3a of a previous article [3] 5 panels in Figure 2a appear to be the same as panels in Figure 2C of a previous article [4] The Editors-in-Chief therefore no longer have confidence in the results and conclusions presented. Pallab Bhattacharya, Anand Kumar Pandey, Sudip Paul and Ranjana Patnaik disagree with this retraction. © The Author(s) under exclusive licence to University of Navarra 2022.